A cohort study of treatment-experienced HIV-1-infected patients treated with raltegravir: factors associated with virological response and mutations selected at failure

Int J Antimicrob Agents. 2013 Jul;42(1):42-7. doi: 10.1016/j.ijantimicag.2013.02.016. Epub 2013 Apr 4.

Abstract

This study aimed to identify factors associated with virological response (VR) to raltegravir (RAL)-containing regimens in 468 treatment-experienced but integrase inhibitor-naive HIV-1 patients receiving a RAL-containing regimen. VR was defined at Month 6 (M6) as HIV-1 RNA viral load (VL) <50 copies/mL. The impacts on VR of baseline integrase mutations, VL, CD4 count, genotypic sensitivity score for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the number of new antiretrovirals used for the first time associated with RAL were investigated. For patients with VL >50 copies/mL at M6, integrase mutations selected were characterised. Median baseline VL was 4.2 log(10)copies/mL (IQR 3.3-4.9 log(10) copies/mL) and CD4 count was 219 cells/mm(3) (IQR 96-368 cells/mm(3)). At M6, 71% of patients were responders. In multivariate analysis, baseline VL and CD4 count and ≥ 2 new antiretrovirals among darunavir, etravirine, maraviroc and enfuvirtide were associated with VR to RAL. Neither HIV-1 subtype nor baseline integrase polymorphisms were associated with VR to RAL. Among 63 failing patients at M6, selection of ≥ 1 change in the integrase gene was observed in 49 (77.8%), and 27/63 (42.9%) were considered as RAL-associated resistance mutations. Factors independently associated with the occurrence of ≥ 1 RAL-associated resistance mutation were VL at failure >3 log(10) and having no new drugs associated with RAL. RAL showed great potency in treatment-experienced patients. The number of new drugs associated with RAL was an important factor associated with VR. HIV-1 subtype and baseline integrase polymorphisms do not influence the RAL VR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Drug Resistance, Viral*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Male
  • Mutation, Missense*
  • Pyrrolidinones / therapeutic use*
  • RNA, Viral / blood
  • Raltegravir Potassium
  • Treatment Failure
  • Viral Load

Substances

  • Anti-HIV Agents
  • Pyrrolidinones
  • RNA, Viral
  • Raltegravir Potassium